Recently, mutation of the FOXL2 gene has been consistently identified in adult
granulosa cell tumors of the ovary. The purpose of this study is to investigate whether the FOXL2 mutation and
mRNA expression have a role in the pathogenesis of juvenile and adult
granulosa cell tumors and influence
tumor progression. Thirty-four adult
granulosa cell tumors and 20 juvenile
granulosa cell tumors were examined for the presence of the FOXL2 (C402G) mutation. Expression levels were studied by quantitative PCR and immunohistochemistry. We found that FOXL2 (C402G) mutation was present in 19/27 (70%) of the adult type
tumors but in none of the juvenile
granulosa cell tumors (0/18). No correlation was encountered between the presence of FOXL2 mutation and various clinicopathologic parameters except for the presence of a different sex-cord component, which was more frequently found in the subgroup of wild-type adult
granulosa cell tumors than in the mutated
tumors. Patients with
tumors harboring the FOXL2 (C402G) mutation had a worse disease-free survival than those with the wild-type gene. Expression levels of FOXL2
mRNA had an impact on disease-free survival in both adult and juvenile
granulosa cell tumors. We also found that the mutated
tumors had a higher immunohistochemical expression of the
FOXL2 protein, and there was a linear correlation between
mRNA and immunohistochemical FOXL2 expression in both adult and juvenile
granulosa cell tumors. Patients with juvenile
granulosa cell tumors and higher
FOXL2 protein expression had worse overall survival and disease-free survival than those with negative or weakly immunoreactive
tumors. Our data suggest that FOXL2 mutation and
mRNA expression are of prognostic importance in both adult and juvenile
granulosa cell tumors.